Complement plays a significant role in the pathogenesis of myocardial ischemia/reperfusion. Studies using anti-complement therapies indicate that limiting the pro-inflammatory action of complement decreases myocardial injury and helps to maintain vascular homeostasis during periods of oxidative stress. (for review, see Collard et al., Mol. Immuno., 1999) Understanding the mechanisms of complement activation on endothelial cells is essential for the development of potent anti-complement compounds. Data generated from this laboratory shows that the mannose binding lectin (MBL) is responsible for initiating the lectin pathway of complement (LCP) on hypoxic/reoxygenated (H/R) endothelial cells. Since de novo protein synthesis and NFkB are involved in complement activation on H/R cells, we hypothesize that a novel MBL ligand is upregulated during the oxidative stress. This research project will identify the MBL ligand on H/R endothelial cells and establish its role in complement activation. Furthermore, the molecular mechanisms of MBL ligand regulation will be characterized and novel therapeutics will be designed based on the specific interactions between MBL and the endothelial MBL ligand.